Bacterial infections are a leading cause of death worldwide even with the many powerful antibiotics available. The number of antibiotic resistant strains has been increasing, and thus, there is an urgent public health need to validate new antibacterial agents. Testing of new agents in a living mouse can be the most accurate way to track organ burden over time. However, serial plating of organs can be limited to a single point in time per animal tested. Bioluminescent imaging (“BLI”) has been shown to be able to qualitatively tract bacterial infection, but it has never been shown to accurately quantify bacterial colony forming units (“CFUs”) in 3D in real time.
Cancer is the second leading cause of death in the United States, but survival is gradually improving due to increasingly sophisticated combinatorial therapies which can include chemotherapy, surgery and radiation. In order to continue the development and optimization of new combinatorial treatment strategies, it can be important to have preclinical studies that can accurately model human cancers and their treatment strategies. Immunotherapy has also rapidly become a promising treatment for cancer. While, BLI has been shown to tract bacterial infections, it cannot quantify or tract immune or cancer cells, in real time, and it cannot monitor the tumor size in response to the therapy. Stem cell research has been shown to aid in the repair of damaged tissue; however, there currently is no tool which can monitor the repair process in the living animal.
In vivo imaging of optical reporters in mice, and other small animals, can provide important information regarding the progression of disease states. For example, cancerous cells in mice can be engineered to express a bioluminescent probe, which can be imaged to show how large the cancers grow, and where it can be located in the animal. While currently there are optical imaging tools that can perform two-dimensional (“2D”) and three-dimensional (“3D”) imaging, no information about the biological significance can be determined. For example, current imaging technologies can provide outputs in physical terms (e.g., photons per sec per cm2), which does not provide information on the biological relevance.
While 2D or planar optical imaging of fluorescence or bioluminescence reporters has been performed in pre-clinical optical imaging, it can only provide relative light intensities at the tissue surface of the animal, which can be dependent on animal size, reporter probe location and imaging time point. Furthermore, a 3D reconstruction of such a light emitting source inside the tissue can provide the light emission density at the origin of light production. However, in 2D and 3D optical imaging, only a physical quantity with physical units (e.g., photons per sec per cm2 or photons per sec per cm3) can be available. Additionally, the physical quantity can often be expressed in relative terms (e.g. fold-changes) with respect to an initial study point. However, currently, there is no information about the actual quantity of biological relevance (e.g., amount of light emitting cancer cells, amount of light-emitting bacteria) that can directly relate to the biological target. In addition, no anatomical reference is currently available.
Thus, it may be beneficial to provide exemplary systems, methods and computer-accessible mediums that can provide fully quantitative information of anatomical structures (e.g., including small animals), that can determine the efficacy of one or more drugs, and which can overcome at least some of the deficiencies described herein above.